peer reviewed | Metconazole (MEZ), a chiral triazole fungicide, produces enantioselective adverse effects in non-target organisms. Among MEZ's isomers, cis-MEZ displays robust antimicrobial properties. Evaluating MEZ and cis-MEZ's toxicity may mitigate fungicide usage and safeguard non-target organisms. Our study evaluated the toxicity of MEZ and its cis-isomers at concentrations of 0.02, 0.2, 2, and 4 mg L−1. We report stereoselectivity and severe cardiovascular defects in zebrafish, including pericardial oedema, decreased heart rate, increased sinus venous and bulbous arteries distances, intersegmental vessel defects, and altered cardiovascular development genes (hand2, gata4, nkx2.5, tbx5, vmhc, amhc, dll4, vegfaa, and vegfc). Further, MEZ significantly increased oxidative stress and apoptosis in zebrafish, primarily in the cardiac region. Isoquercetin, an antioxidant found in plants, partially mitigates MEZ-induced cardiac defects. Furthermore, MEZ upregulated the Wnt/β-catenin pathway genes (wnt3, β-catenin, axin2, and gsk-3β) and β-catenin protein expression. Inhibitor of Wnt Response-1 (IWR-1) rescued MEZ-induced cardiotoxicity. Our findings highlight oxidative stress, altered cardiovascular development genes, and upregulated Wnt/β-catenin signaling as contributors to cardiovascular toxicity in response to MEZ and cis-MEZ treatments. Importantly, 1R,5S-MEZ exhibited greater cardiotoxicity than 1S,5R-MEZ. Thus, our study provides a comprehensive understanding of cis-MEZ's cardiovascular toxicity in aquatic life. © 2024 Elsevier Ltd

Particulate-filtering respirators (PFRs) have been recommended as a practical personal-level intervention to protect individuals from the health effects of particulate matter exposure. However, the cardiovascular benefits of PFRs including improvements in key surrogate endpoints remain unclear. We performed a systematic review and meta-analysis of randomized studies (wearing versus not wearing PFRs) reporting the effects on blood pressure (BP) and heart rate variability (HRV). The search was performed on January 3, 2022 to identify published papers until this date. We queried three English databases, including PubMed, Web of Science Core Collection and Scopus. Of 527 articles identified, eight trials enrolling 312 participants (mean age ± standard deviation: 36 ± 19.8; 132 female) met our inclusion criteria for analyses. Study participants wore PFRs from 2 to 48 h during intervention periods. Wearing PFRs was associated with a non-significant pooled mean difference of −0.78 mmHg (95% confidence interval [CI]: −2.06, 0.50) and −0.49 mmHg (95%CI: −1.37, 0.38) in systolic and diastolic BP (SBP and DBP). There was a marginally significant reduction of mean arterial pressure (MAP) by nearly 1.1 mmHg (95%CI: −2.13, 0.01). The use of PFRs was associated with a significant increase of 38.92 ms² (95%CI: 1.07, 76.77) in pooled mean high frequency (power in the high frequency band (0.15–0.4 Hz)) and a reduction in the low (power in the low frequency band (0.04–0.15Hz))-to-high frequency ratio [−0.14 (95%CI: −0.27, 0.00)]. Other HRV indices were not significantly changed. Our meta-analysis demonstrates modest or non-significant improvements in BP and many HRV parameters from wearing PFRs over brief periods. However, these findings are limited by the small number of trials as well as variations in experimental designs and durations. Given the mounting global public health threat posed by air pollution, larger-scale trials are warranted to elucidate more conclusively the potential health benefits of PFRs.

Microplastics are sometimes considered not harmful at environmentally relevant concentrations. Yet, such studies were conducted under standard thermal conditions and thereby ignored the impacts of higher mean temperatures (MT), and especially daily temperature fluctuations (DTF) under global warming. Moreover, an evolutionary perspective may further benefit the future risk assessment of microplastics under global warming. Here, we investigated the effects of two generations of exposure to an environmentally relevant concentration of polystyrene microplastics (5 μg L⁻¹) under six thermal conditions (2 MT × 3 DTF) on the life history, physiology, and behaviour of Daphnia magna. To assess the impact of thermal evolution we thereby compared Daphnia populations from high and low latitudes. At the standard ecotoxic thermal conditions (constant 20 °C) microplastics almost had no effect except for a slight reduction of the heartbeat rate. Yet, at the challenging thermal conditions (higher MT and/or DTF), microplastics affected each tested variable and caused an earlier maturation, a higher fecundity and intrinsic growth rate, a decreased heartbeat rate, and an increased swimming speed. These effects may be partly explained by hormesis and/or an adaptive response to stress in Daphnia. Moreover, exposure to microplastics at the higher mean temperature increased the fecundity and intrinsic growth rate of cold-adapted high-latitude Daphnia, but not of the warm-adapted low-latitude Daphnia, suggesting that thermal evolution in high-latitude Daphnia may buffer the effects of microplastics under future warming. Our results highlight the critical importance of DTF and thermal evolution for a more realistic risk assessment of microplastics under global warming.

Several studies highlighted the ubiquitous presence of ibuprofen and aluminum in the aquatic environment around the world and demonstrated their potential to induce embryotoxic and teratogenic defects on aquatic species individually. Although studies that evaluate developmental alterations induced by mixtures of these pollutants are scarce; and, since environmental contamination presented in the form of a mixture of toxicants with different chemical properties and toxicity mechanisms capable of generating interactions; the objective of this study was to evaluate the developmental defects, teratogenic alterations, and oxidative stress induced by individual forms and the mixture of ibuprofen (IBU) and aluminum (Al) on zebrafish embryos. Oocytes exposed to environmentally relevant concentrations of IBU (0.1–20 μg L-1) and Al (0.01–8 mg L-1) and one binary mixture. The LC50 and EC50 were obtained to calculate the teratogenic index (TI). The IBU LC50, EC50, and TI were 8.06 μg L-1, 2.85 μg L-1 and 2.82. In contrast, Al LC50 was 5.0 mg L-1with an EC50 of 3.58 mg L-1 and TI of 1.39. The main alterations observed for individual compounds were hatching alterations, head malformation, skeletal deformities, hypopigmentation, pericardial edema, and heart rate impairment. The mixture also showed significant delays to embryonic development. Moreover, oxidative stress biomarkers of cellular oxidation and antioxidant defenses at 72 and 96 hpf significantly increased. Results show that environmentally relevant concentrations of ibuprofen (IBU), aluminum (Al), and their mixture promote a series of developmental defects, teratogenic effects, and oxidative disruption on D. rerio embryos, and the interaction of both substances altered the response. In conclusion, morphological and biochemical tests are suitable tools for assessing the health risk of aquatic wildlife by exposure to individual and mixed pollutants in freshwater bodies.

A large number of toxicity studies report abnormalities in early life-stage (ELS) fish that are described here as a sublethal toxicity syndrome (TxSnFELS) and generally include a reduced heart rate, edemas (yolk sac and cardiac), and a variety of morphological abnormalities. The TxSnFELS is very common and not diagnostic for any chemical or class of chemicals. This sublethal toxicity syndrome is mostly observed at high exposure concentrations and appears to be a baseline, non-specific toxicity response; however, it can also occur at low doses by specific action. Toxicity metrics for this syndrome generally occur at concentrations just below those causing mortality and have been reported for a large number of diverse chemicals. Predictions based on tissue concentrations or quantitative-structure activity relationship (QSAR) models support the designation of baseline toxicity for many of the tested chemicals, which is confirmed by observed values. Given the sheer number of disparate chemicals causing the TxSnFELS and correlation with QSAR derived partitioning; the only logical conclusion for these high-dose responses is baseline toxicity by nonspecific action and not a lock and key type receptor response. It is important to recognize that many chemicals can act both as baseline toxicants and specific acting toxicants likely via receptor interaction and it is not possible to predict those threshold doses from baseline toxicity. We should search out these specific low-dose responses for ecological risk assessment and not rely on high-concentration toxicity responses to guide environmental protection. The goal for toxicity assessment should not be to characterize toxic responses at baseline toxicity concentrations, but to evaluate chemicals for their most toxic potential. Additional aspects of this review evaluated the fish ELS teratogenic responses in relation to mammalian oral LD50s and explored potential key events responsible for baseline toxicity.

Diclofop-methyl (DM) is one of the most widely used herbicides in agriculture production and has been frequently detected in both freshwater and environments, even agricultural products. However, the potential toxic effects of DM on organisms and the underlying mechanisms are still poorly understood. In this study, we utilized zebrafish to evaluate the toxicity of DM during the cardiovascular developmental process. Exposure of zebrafish embryos to 0.75, 1.0 and 1.25 mg/L DM induced cardiac defects, such as pericardial edema, slow heart rate and long SV-BA distance but the vascular development in zebrafish larvae was not influenced by DM treatment. The expression of cardiac-related genes were disordered and DM exposure initiated disordering cardiogenesis from the period of precardiac mesoderm formation. Moreover, the apoptosis and proliferation of cardiomyocytes were not influenced but the levels of oxidative stress were upregulated by DM exposure. Fullerenes and astaxanthin was able to rescue cardiac defects caused by DM via downregulating oxidative stress. Wnt signaling was downregulated after DM treatment and activation of Wnt signaling could rescue cardiac defects. Therefore, our results suggest that DM has the potential to induce cardiac developmental toxicity through upregulation of Wnt-Mediated (reactive oxygen species) ROS generation in zebrafish larvae.

Indoor air pollution is associated with numerous adverse health outcomes. Air purifiers are widely used to reduce indoor air pollutants. Ionization air purifiers are becoming increasingly popular for their low power consumption and noise, yet its health effects remain unclear. This randomized, double-blind crossover study is conducted to explore the cardiorespiratory effects of ionization air purification among 44 children in Beijing. Real or sham purification was performed in classrooms for 5 weekdays. Size-fractionated particulate matter (PM), black carbon (BC), ozone (O₃), and negative air ions (NAI) were monitored, and cardiorespiratory functions were measured. Mixed-effect models were used to establish associations between exposures and health parameters. Real purification significantly decreased PM and BC, e.g. PM₀.₅, PM₂.₅, PM₁₀ and BC were decreased by 48%, 44%, 34% and 50%, respectively. O₃ levels were unchanged, while NAI was increased from 12 cm⁻³ to 12,997 cm⁻³. Real purification was associated with a 4.4% increase in forced exhaled volume in 1 s (FEV₁) and a 14.7% decrease in fractional exhaled nitrogen oxide (FeNO). However, heart rate variability (HRV) was altered negatively. Interaction effects of NAI and PM were observed only on HRV, and alterations in HRV were greater with high NAI. Ionization air purifier could bring substantial respiratory benefits, however, the potential negative effects on HRV need further investigation.

As a new type of pollutant, fluoroquinolones (FQs) antibiotics are ubiquitous in environment and have some threat to human health and ecological environment. Their ecological toxicity to the environment urgently need to be assessed. Therefore, we firstly explored the toxic effects and possible mechanism of cardiovascular toxicity induced by gatifloxacin (GTFX) and ciprofloxacin (CPFX) using zebrafish model. After 24 h exposure, the zebrafish treated with GTFX showed pericardial edema which was further investigated by histopathological examination, while CPFX exposure did not induce morphological abnormalities. However, both of them induced cardiac dysfunction, such as decreased heart rate and cardiac output which was showed a positive correlation with the concentration. To better understand the possible molecular mechanisms underlying cardiovascular toxicity in zebrafish, we investigated the transcriptional level of genes related to calcium signaling pathway and cardiac muscle contraction. The results indicated that the expression of ATPase (atp2a1l) and cardiac troponin C (tnnc1a) genes were significantly inhibited, the expression of calcium channel (cacna1ab) gene showed slight promoted trend after CPFX exposure. For zebrafish treated with GTFX, the expression of atp2a1l genes was also significantly inhibited, while the expression of tnnc1a genes was slightly inhibited and cacna1ab genes expression had no obvious effect. The present study firstly revealed that GTFX exposure can induce morphological and functional abnormalities on the cardiovascular system of zebrafish. Though CPFX exposure did not induce morphological abnormalities, the function of cardiovascular system was still damaged. Mechanistically, this toxicity might result from the pressure of down-regulation of genes associated with calcium signaling pathway and cardiac muscle contraction. The results of this study can provide a valuable theoretical basis for the establishment of FQs environmental quality standards in water environment, environmental drug regulation and risk management.

Dichlorvos (2,2-dichlorovinyl-dimethylphosphate), an organophosphorus pesticide used for indoor insect and livestock parasite control, is among the most common commercially available pesticides. However, there are significant concerns over its toxicity, especially due to its relative stability in water, soil, and air. Zebrafish, an important developmental model, has been used for studying the effects of toxic compounds. The aim of this study was to evaluate the exposure to dichlorvos at early life stages (1 h postfertilization - 7 days postfertilization) in the zebrafish and its toxicological effects during the development, through morphological (7 days postfertilization), locomotor and social behavior analysis (7, 14, 30, 70, and 120 days postfertilization). Dichlorvos (1, 5, and 10 mg/L) exposure reduced the body length and heartbeat rate at 7 days postfertilization (dpf), as well as the surface area of the eyes (5 and 10 mg/L). The avoidance behavior test showed a significant decrease in escape responses at 7 (1, 5, and 10 mg/L) and 14 (5 and 10 mg/L) dpf zebrafish. The evaluation of larval exploratory behavior showed a reduction in distance traveled, mean speed (1, 5, and 10 mg/L) and time mobile (10 mg/L) between control and dichlorvos groups. In addition, the analysis performed on adult animals showed that the changes in distance traveled and mean speed remained reduced in 30 (1, 5, and 10 mg/L) and 70 dpf (5 and 10 mg/L), recovering values similar to the control at 120 dpf. The social behavior of zebrafish was not altered by exposure to dichlorvos in the early stages of development. Thus, the exposure to organophosphorus compounds at early stages of development induces an increased susceptibility to behavioral and neuronal changes that could be associated with several neurodegenerative diseases.

The ubiquity of microplastics in the world's ocean has aroused great concern. However, the ecological effects of microplastics at environmentally realistic concentrations are unclear. Here we showed that exposure of marine medaka (Oryzias melastigma) to environmentally relevant concentrations of 10 μm polystyrene microplastics for 60 days not only led to microplastic accumulation in the gill, intestine, and liver, but also caused oxidative stress and histological changes. Moreover, 2, 20, and 200 μg/L microplastics delayed gonad maturation and decreased the fecundity of female fish. Alterations of the hypothalamus-pituitary-gonadal (HPG) axis were investigated to reveal the underlying mechanisms, and gene transcription analysis showed that microplastic exposure had significantly negative regulatory effects in female HPG axis. Transcription of genes involved in the steroidogenesis pathway in females were also downregulated. This disruption resulted in decreased concentrations of 17β-estradiol (E₂) and testosterone (T) in female plasma. Furthermore, parental exposure to 20 μg/L microplastics postponed the incubation time and decreased the hatching rate, heart rate, and body length of the offspring. Overall, the present study demonstrated for the first time that environmentally relevant concentrations of microplastics had adverse effects on the reproduction of marine medaka and might pose a potential threat to marine fish populations.